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As the better alternative to complex protein\u2013lipid formulations it was recently established that the C-terminal region of the ApoA-I protein singly improves the metabolic control and prevents formation of atherosclerotic plaques. Additional investigations of peptides based on the ApoA-I structure may lead to novel anti-diabetic drugs. We here investigate a short peptide (33mer, RG33) that corresponds to the two last helical segments (aa 209\u2013241) of the ApoA-I structure (so-called class Y-helices which forms amphipathic helices) for stability and solubility in serum, for in vitro cholesterol efflux capability, and for providing in vivo glucose control in an insulin resistant mouse model. The RG33 peptide efficiently solubilizes lipid-vesicles, and promotes the efflux of cholesterol from cultured macrophages. The efflux capacity is significantly increased in the presence of lipids compared to non-lipidated RG33. Finally, acute treatment with the RG33 peptide significantly improves the glucose clearance capacity of insulin resistant mice. The impact of the RG33 peptide on glucose control and cholesterol transport, as well as the physicochemical properties, makes it a good candidate for translational exploration of its therapeutic potential in diabetes treatment.<\/jats:p>","DOI":"10.1038\/s41598-020-75232-0","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T10:03:14Z","timestamp":1603360994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A short peptide of the C-terminal class Y helices of apolipoprotein A-I has preserved functions in cholesterol efflux and in vivo metabolic control"],"prefix":"10.1038","volume":"10","author":[{"given":"Shelley J.","family":"Edmunds","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebeca","family":"Li\u00e9bana-Garc\u00eda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin G.","family":"Stenkula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens O.","family":"Lagerstedt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"75232_CR1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.diabres.2017.03.024","volume":"128","author":"K Ogurtsova","year":"2017","unstructured":"Ogurtsova, K. et al. 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There are no other disclosures by KGS and JOL. The other authors have no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18070"}}